出乎意料:曲安奈德引起的暴发性心肌细胞毒性损伤。

IF 3.2 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Annie J Tsay, Mohan Satish, Elizabeth Corley, Ashley Ezema, Neisha DeJesus, Stephen Wisely, Eileen McAleer, Chen Zhang, Su Yuan, Edwin Homan, Jennifer E Liu, Jonathan W Weinsaft, Sandra D'Angelo, Stephanie A Feldman, Angel T Chan
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引用次数: 0

摘要

背景:曲贝替丁(Tbt)是一种烷化剂,用于治疗一线药物治疗失败后的软组织肉瘤。虽然蒽环类药物暴露后接受 Tbt 治疗可能会发生心肌病,但在与 Tbt 相关的其他全身细胞毒性背景下,Tbt 引发的暴发性心肌细胞毒性损伤尚未见报道:51 岁女性,患有高血压、高脂血症和转移性白肌瘤,尽管接受了包括多柔比星在内的多线化疗,但病情仍有进展。发病前 5 天,她开始服用曲贝替丁(Tbt),并出现发热、肌痛、关节痛和心悸症状。据报道,横纹肌溶解症、急性肾损伤和肝损伤与 Tbt 治疗有关,因此她入院接受治疗。基线心电图(ECG)显示窦性心动过速,伴有非特异性T波改变,经胸超声心动图(TTE)无异常。然而,在住院的第 3 天,遥测记录到一次无症状的持续单形室性心动过速,心率为每分钟 150 次。12 导联心电图显示新的室间隔 T 波倒置。实验室检查显示 hs-TnI 水平不断升高(峰值为 37,933ng/L),血清标志物显示多器官功能衰竭。考虑到类固醇在治疗多器官结核毒性方面的作用,医生开始使用类固醇。由于急性肾功能衰竭,为排除心肌炎而进行的心脏核磁共振检查和为排除阻塞性冠状动脉疾病而进行的左心导管检查均被放弃。进行了右心导管检查和心内膜活检,发现心脏充盈压和指数正常。病理结果显示,细胞质空泡表明药物引起了心肌细胞毒性。连续的超声心动图显示双心室功能保持正常。尽管在重症监护室接受了最大程度的支持性治疗,但患者的临床状况仍因多个器官衰竭而恶化。她最终去世,但拒绝进行尸检:结论:这是首例报告的开始使用 Tbt 后出现暴发性心肌损伤的病例,组织学证据显示该药物诱发了心肌细胞毒性。虽然目前还不清楚蒽环类药物是否会加重本病例中的 Tbt 细胞毒性损伤,但这是有可能的;Tbt 引起的心脏毒性从亚临床到暴发性不等。鉴于 Tbt 在难治性高级别肉瘤中的应用越来越多,提高对其毒性特征的认识将改善早期发现和治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expect the unexpected: fulminant myocardial cytotoxic Injury from Trabectedin.

Background: Trabectedin (Tbt) is an alkylating agent prescribed for soft tissue sarcomas after treatment failure of first line agents. While cardiomyopathy can occur with Tbt treatment after anthracycline exposure, Tbt-induced fulminant myocardial cytotoxic injury in the setting of other systemic cytotoxicity associated with Tbt has not been reported.

Case presentation: 51-year-old female with hypertension, hyperlipidemia, metastatic leiomyosarcoma with progression of disease despite several lines of chemotherapy including doxorubicin-based therapy was started on Trabectedin (Tbt) 5 days prior to presentation with symptoms of fever, myalgias, arthralgias, and palpitations. She was admitted for management of rhabdomyolysis, acute kidney and liver injuries which were reportedly known to be associated with Tbt treatment. A baseline electrocardiogram (ECG) revealed sinus tachycardia with non-specific T-wave changes, and a transthoracic echocardiogram (TTE) was unremarkable. However, on day 3 of hospitalization, an episode of asymptomatic sustained monomorphic ventricular tachycardia with a heart rate of 150 beats per minute was captured on telemetry. A 12-lead ECG revealed new septal T-wave inversions. Labs revealed rising hs-TnI levels (peak at 37,933ng/L) and serum markers suggested multi-organ failure. Steroids were initiated given its role in treating multi-organ Tbt-induced toxicity. A cardiac MRI to rule out myocarditis and left heart catheterization to rule out obstructive coronary artery disease were forgone due to acute renal failure. A right heart catheterization with an endomyocardial biopsy was performed revealing normal cardiac filling pressures and indices. Pathology showed cytoplasmic vacuoles indicating drug-induced myocardial cytotoxicity. Serial echocardiograms revealed preserved biventricular function. The patient's clinical condition deteriorated with multi-organ failure despite maximal supportive care in the intensive care unit. She ultimately passed away, and an autopsy was declined.

Conclusion: This is the first reported case of fulminant myocardial injury after initiation of Tbt with histologic evidence of drug-induced myocardial cytotoxicity. While it is unclear if anthracyclines potentiate Tbt cytotoxic injury as in this case, it is plausible; and that Tbt-induced cardiotoxicity ranges from subclinical to fulminant. Given increasing use of Tbt in refractory high-grade sarcomas, raising awareness of its toxicity profile will improve early detection and outcomes.

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来源期刊
Cardio-oncology
Cardio-oncology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
5.00
自引率
3.00%
发文量
17
审稿时长
7 weeks
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